The toxic effects on cardiac myocytes of tyledoside F, a cumulative neurotoxic cardiac glycoside isolated from Tylecodon grandiflorus.
To investigate the cardiac cellular effects of tyledoside F, a cumulative neurotoxic bufadienolide and ouabain, a non-cumulative cardenolide, the whole-cell clamp method was used to measure the Na-K pump current after the Na-K pump had been activated by high intracellular Na2+. The toxic effects of tyledoside F and ouabain on cardiac myocytes were also investigated by observing the effect of the Ca2+ overload on the variability of myocytes during a period of 75 min. From the results it is clear that there are similarities in the direct effects of tyledoside F and ouabain on the Na-K pump. It was found that ouabain inhibited the Na-K pump current more than that of tyledoside F. With regard to Ca2+ overload, there are differences in their mode of production of Ca2+ overload because cinnarizine protects the myocytes against ouabain-induced Ca2+ overload but not against tyledoside-induced Ca2+ overload. This study shows that with the whole-cell clamp technique tyledoside F inhibited the Na-K pump in a manner similar to inhibition of the pump by ouabain. Viability studies with myocytes indicated that tyledoside F also has other effects which are different from these of ouabain.
van Rooyen
J M
JM
Department of Physiology, P.U. for C.H.E., Potchefstroom, Republic of South Africa.
van der Walt
J J
JJ
D000818:Animals; D001693:Biological Transport, Active; D002018:Bufanolides / Q000633:toxicity*; D002301:Cardiac Glycosides / Q000737:chemistry / Q000633:toxicity*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000737:chemistry / Q000633:toxicity; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002018:Bufanolides; D002301:Cardiac Glycosides; D010042:Ouabain; D012964:Sodium; D011188:Potassium